Endo Pharmaceutical Inc.v.DepoMed, Inc.

Patent Trial and Appeal Board

Sep 16, 2015

10029134 (P.T.A.B. Sep. 16, 2015)

Trials@uspto.gov Paper 68
Tel: 571-272-7822 Entered: September 16, 2015

UNITED STATES PATENT AND TRADEMARK OFFICE
_______________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_______________

ENDO PHARMACEUTICALS, INC.,
Petitioner,

v.

DEPOMED, INC.,
Patent Owner.
_______________

Case IPR2014-00652
Patent 6,723,340 B2
_______________

Before GRACE KARAFFA OBERMANN, GEORGIANNA W. BRADEN,
and TINA E. HULSE, Administrative Patent Judges.

BRADEN, Administrative Patent Judge.

FINAL WRITTEN DECISION
35 U.S.C. § 318 and 37 C.F.R. § 42.73

IPR2014-00652
Patent 6,723,340 B2

2
I. INTRODUCTION
We have jurisdiction to hear this inter partes review under 35 U.S.C.
§ 6(c). This Final Written Decision is issued pursuant to 35 U.S.C. § 318(a)
and 37 C.F.R. § 42.73. For the reasons that follow, we determine that
Petitioner has shown by a preponderance of the evidence that claims 1, 3–5,
and 10–13 of U.S. Patent No. 6,723,340 B2 (Ex. 1001, “the ’340 patent”) are
unpatentable. We also address the parties’ Motions to Exclude.
A. Procedural History
Endo Pharmaceuticals, Inc. (“Petitioner”) filed a Corrected Petition
(Paper 5, “Pet.”) to institute an inter partes review of claims 1–5 and 10–13
of the ’340 patent pursuant to 35 U.S.C. § 311. Depomed, Inc. (“Patent
Owner”) filed a Preliminary Response (Paper 11, “Prelim. Resp.”). Pursuant
to 35 U.S.C. § 314(a), we instituted an inter partes review of claims 1, 3–5,
and 10–13 on the following grounds alleged in the Petition.
Reference(s) Basis Claims challenged
Shell 1998 Publication1 § 103 1, 3–5, and 10–13
Shell 1998 Publication and
Papadimitriou2
§ 103 1, 3–5, and 10–13
Edgren3 and Papadimitriou § 103 1, 3–5, and 10–13
Paper 12 (“Dec. to Inst.”), 29.

1 WO 1998/55107, PCT/US98/11302, issued Dec. 10, 1998 (Ex. 1003,
“Shell 1998 Publication”).
2 Papadimitriou E., et. al., “Swelling studies on mixtures of two hydrophilic
excipients,” S.T.P. Pharma. Sciences Vol. 3, issue 3, pages 232–236 (Jun.
1993) (Ex. 1007, “Papadimitriou”).
3 U.S. Patent No. 4,871,548, issued Oct. 3, 1989 (Ex. 1006, “Edgren”).
IPR2014-00652
Patent 6,723,340 B2

3
After institution of trial, Patent Owner filed a Patent Owner Response
(Paper 25, “PO Resp.”),4 to which Petitioner filed a Reply (Paper 41,
“Reply”).
In addition, Petitioner filed a Motion to Exclude. Paper 51 (“Pet. Mot.
Exclude”). Patent Owner filed an Opposition to Petitioner’s Motion to
Exclude (Paper 56, “PO Exclude Opp.”), and Petitioner filed a Reply (Paper
58, “Pet. Exclude Reply”). Patent Owner also filed a Motion to Exclude.
Paper 53 (“PO Mot. Exclude”). Petitioner filed an Opposition to Patent
Owner’s Motion to Exclude (Paper 54, “Pet. Exclude Opp.”), and Patent
Owner filed a Reply (Paper 59, “PO Exclude Reply”). Patent Owner also
filed observations on the cross-examination of Petitioner’s declarant
(Paper 52), to which Petitioner filed a response (Paper 55).
An oral argument was held on June 15, 2015. A transcript (“Tr.”) of
the oral argument is included in the record.5 Paper 67.
B. Related Proceedings
Petitioner informs us that the ’340 patent is involved in the following
co-pending federal district court cases: Depomed, Inc. v. Actavis Elizabeth
LLC, 3:12-cv-01358-JAP-TJB (D.N.J.); Depomed, Inc. v. Endo Pharms.

4 Patent Owner filed a confidential Patent Owner Response (Paper 24) and a
public Patent Owner Response (Paper 25) to which Petitioner filed a
confidential Reply (Paper 40) and a public Reply (Paper 41). All citations in
this Final Written Decision are to the public Patent Owner Response (Paper
25) and public Petitioner Reply (Paper 41).
5 The parties filed joint Objections to Demonstrative Exhibits. Paper 64. In
this Final Written Decision, we rely directly on the arguments presented
properly in the parties’ briefs and the evidence of record. The demonstrative
exhibits were only considered to the extent they are consistent with those
arguments and evidence, therefore, the objections are overruled.
IPR2014-00652
Patent 6,723,340 B2

4
Inc., 3:13-cv-02467-JAP-TJB (D.N.J.); Depomed, Inc. v. Purdue Pharma
L.P., 3:13-00571 JAP-TJB (D.N.J.); Depomed, Inc. v. Zydus Pharm. (USA),
Inc., 3:12-cv-02813-JAP-TJB (D.N.J.); Depomed, Inc. v. Sun Pharma
Global FZE, 3:11-CV-03553 (D.N.J.); Depomed, Inc. v. Impax Labs., Inc.,
3:12-CV-02154 (D.N.J.); Depomed, Inc. v. Lupin Pharms., Inc., 4:09-CV-
05587. Pet. 1. In addition, Petitioner filed several petitions requesting inter
partes review of related patents. Id. at 2. Those cases are: IPR2014-00651
(involving the ’340 patent); IPR2014-00653 and IPR2014-00654 (involving
U.S. Patent No. 6,340,475 B2); and IPR2014-00655 and IPR2014-00656
(involving U.S. Patent No. 6,635,340 B2). Id. We consolidated the oral
hearings for the three instituted proceedings: IPR2014-00652, IPR2014-
00654, and IPR2014-00656. See Paper 57.
C. The ’340 Patent
The ’340 patent relates to drugs formulated as unit oral dosage forms
by incorporating them into matrices formed of a combination of
poly(ethylene oxide) (“PEO”) and hydroxypropyl methylcellulose
(“HPMC”). Ex. 1001, Abstract. The matrices swell upon exposure to
gastric fluid to a size large enough to promote retention (id. at Abstract,
11:66–67) and release the drugs into the stomach or upper gastrointestinal
(“GI”) tract, rather than the lower portions of the GI tract (id. at 1:10–13).
The ’340 patent discloses that when nutritive materials enter the stomach,
the stomach is in “fed mode” and the pyloric sphincter is open partially. Id.
at 1:62–2:9. During the “fed mode,” particles exceeding about 1 cm in size
are retained in the stomach, because they are too large to pass through a
partially open pyloric sphincter. Id. at 2:5–11.
IPR2014-00652
Patent 6,723,340 B2

5
PEO and HPMC are both water-swellable polymers. Id. at 3:11–15,
3:23–25, 10:38–46, Fig. 5. According to the ’340 patent, the swelling and
controlled release properties of PEO are balanced with the predictable
erosion behavior of HPMC, which modulates the extent and progress of the
overall swelling of a combined polymeric matrix. Id. at 3:40–43. The ’340
patent discloses that the competing, yet complementary, actions of swelling
and erosion allow for slower and more even disintegration compared to
tablets made solely or primarily with PEO. Id. at 3:50–54.
Certain embodiments in the specification of the ’340 patent teach that
for highly soluble drugs, the PEO component of the matrix limits the initial
release of the drug while imparting gastric retention through swelling. Id. at
4:5–7. In other embodiments, the specification teaches that for sparingly
soluble drugs, the HPMC component of the matrices prevents premature
release of the drugs by retarding the erosion rate of the PEO, while the PEO
provides gastric retention. Id. at 4:10–14.
The specification further teaches that prolonged release rates reduce
the problem of transient overdosing, and control the dosage to safer and
more effective levels over an extended period of time. Id. at 7:44–49.
D. Illustrative Claim
As noted above, an inter partes review was instituted as to claims 1,
3–5, and 10–13 of the ’340 patent, of which claim 1 is the only independent
claim. Claim 1 is illustrative of the challenged claims and is reproduced
below (with paragraphing):
1. A controlled-release tablet for releasing a drug into at least a portion of
a region defined by the stomach and the upper gastrointestinal tract,
said tablet comprising a solid monolithic matrix with said drug
dispersed therein,
IPR2014-00652
Patent 6,723,340 B2

6
said matrix comprising a combination of poly(ethylene oxide) and
hydroxypropyl methylcellulose at a weight ratio that causes said
matrix to swell upon contact with gastric fluid to a size large
enough to provide gastric retention,
wherein said drug has a solubility in water that exceeds one part of
said drug per ten parts of water, by weight, and
wherein said poly(ethylene oxide) has a viscosity average molecular
weight of from about 2,000,000 to about 10,000,000 daltons, and
wherein said hydroxypropyl methylcellulose has a
viscosity of from about 4,000 centipoise to about 200,000
centipoise, measured as a 2% solution in water.
Id. at 11:60–12:9.

II. DISCUSSION
A. Claim Construction
In an inter partes review, claim terms in an unexpired patent are
interpreted according to their broadest reasonable construction in light of the
specification of the patent in which they appear. 37 C.F.R. § 42.100(b); see
also In re Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1278–79 (Fed. Cir.
2015) (“Congress implicitly approved the broadest reasonable interpretation
standard in enacting the AIA,” and “the standard was properly adopted by
PTO regulation.”), reh’g en banc denied, 793 F.3d 1297 (Fed. Cir. 2015).
Under that standard, and absent any special definitions, we give claim terms
their ordinary and customary meaning, as would be understood by one of
ordinary skill in the art at the time of the invention. In re Translogic Tech.,
Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007).
In the Decision to Institute, we construed the terms “monolithic
matrix,” “to swell upon contact with gastric fluid to a size large enough to
provide gastric retention,” and “gastric fluid” in independent claim 1. See
Dec. to Inst. 6–10. During the course of the trial, neither party challenged
IPR2014-00652
Patent 6,723,340 B2

7
our constructions of these claim terms. PO Resp. 11–12. Thus, we see no
reason to alter the constructions of these claim terms as set forth in the
Decision to Institute, and we incorporate our previous analysis for purposes
of this decision. Therefore, for the reasons set forth in the Decision to
Institute, we interpret various claim terms of the ’340 patent as follows:
Term(s) Interpretation
“monolithic matrix” “a matrix constructed as a single piece”
“to swell upon contact with
gastric fluid to a size large
enough to provide gastric
retention”
“to increase in size upon contact with gastric
fluid such that the tablet remains in the
stomach”
“gastric fluid” “both the fluid in the stomach and simulated
or artificial fluids recognized by those skilled
in the art as a suitable model for the fluid of
the human stomach”
See Dec. to Inst. 6–10.
All other claim terms will be given their ordinary and customary
meaning, as would be understood by one of ordinary skill in the art at the
time of the invention.
B. Principles of Law
To prevail in its challenges to the patentability of the claims, a
petitioner must establish facts supporting its challenges by a preponderance
of the evidence. 35 U.S.C. § 316(e); 37 C.F.R. § 42.1(d). A claim is
unpatentable under 35 U.S.C. § 103(a) if the differences between the subject
matter sought to be patented and the prior art are such that the subject matter
as a whole would have been obvious at the time the invention was made to a
person having ordinary skill in the art to which said subject matter pertains.
IPR2014-00652
Patent 6,723,340 B2

8
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007). The question of
obviousness is resolved on the basis of underlying factual determinations,
including: (1) the scope and content of the prior art; (2) any differences
between the claimed subject matter and the prior art; (3) the level of skill in
the art; and (4) objective evidence of nonobviousness, i.e., secondary
considerations. See Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
We analyze the instituted grounds of unpatentability in accordance
with the above-stated principles.
C. Level of Ordinary Skill in the Art
In determining whether an invention would have been obvious at the
time it was made, we consider the level of ordinary skill in the pertinent art
at the time of the invention. Graham, 383 U.S. at 17. “The importance of
resolving the level of ordinary skill in the art lies in the necessity of
maintaining objectivity in the obviousness inquiry.” Ryko Mfg. Co. v. Nu-
Star, Inc., 950 F.2d 714, 718 (Fed. Cir. 1991).
Petitioner contends that a person of ordinary skill in the art at the time
of the ’340 patent would have “at least a bachelor’s degree in chemistry,
chemical engineering, pharmaceutical science and/or material science, as
well as substantial experience (for example, at least several years of
industrial or academic work) in the design and/or development of controlled
release oral drug dosage forms.” Pet. 10 (citing Ex. 1008). Petitioner
further contends that a person of ordinary skill in the art “would also need to
possess, or have access to, the skill of a pharmacologist familiar with how
such medicines work in the body.” Id. According to Petitioner’s declarant,
Dr. Clive Wilson, a person of ordinary skill in the art “would have
experience, or access to other persons with experience, in the field of
IPR2014-00652
Patent 6,723,340 B2

9
pharmacology, with particular emphasis on the pharmacokinetics and
pharmacodynamics of oral drugs absorbed in the GI tract.” Ex. 1008 ¶ 26.
Patent Owner does not disagree with Petitioner’s assertion regarding
the level of skill in the art, nor does Patent Owner offer its own explanation
regarding who would qualify as a person of ordinary skill in the art relevant
to the ’340 patent offer. PO Resp. 11.
Based on our review of the ’340 patent and the types of problems and
solutions described in the ’340 patent and cited prior art, we conclude a
person of ordinary skill in the art at the time of the ’340 patent would have a
Bachelor’s degree in chemistry or a similar discipline, and at least several
years of work experience in the design and/or development of controlled
release oral drug dosage forms. We further note that the applied prior art
reflects the appropriate level of skill at the time of the claimed invention.
See Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001).
D. Alleged Obviousness of Claims 1, 3–5, and 10–13 in View of the
Shell 1998 Publication
Petitioner alleges that claims 1, 3–5, and 10–13 of the ’340 patent are
unpatentable under 35 U.S.C. § 103 in view of the Shell 1998 publication.
Pet. 25–28. Patent Owner disputes Petitioner’s position, arguing that
although the Shell 1998 Publication discloses the use of both PEO and
HPMC alone, it does not disclose, teach, or suggest the combination of PEO
and HPMC as required by the challenged claims. PO Resp. 13. We have
reviewed the Petition, the Patent Owner Response, and Petitioner’s Reply, as
well as the relevant evidence discussed in those papers. For reasons that
follow, we determine that Petitioner has shown by a preponderance of the
evidence that claims 1, 3–5, and 11–13 of the ’340 patent are unpatentable in
view of the Shell 1998 publication. We also determine Petitioner has not
IPR2014-00652
Patent 6,723,340 B2

10
shown by a preponderance of the evidence that claim 10 would have been
obvious in view of the Shell 1998 publication.
1. Overview of the Shell 1998 Publication
The Shell 1998 Publication discloses drugs formulated as unit oral
dosage forms by incorporating them into polymeric matrices that can be
compressed into tablets. Ex. 1003, Abstract. The dosage forms are solid
prior to administration to a patient, water-swellable, and gastric retentive in a
fed mode (a state triggered by food ingestion that lasts for a period of time).
Id. at 2:23–32, 3:2–5. The Shell 1998 Publication specifically discloses
polymeric matrices made from (i) cellulose polymers and their derivatives,
(ii) polysaccharides and their derivatives, (iii) polyaklylene oxides, and (iv)
crosslinked polyacrylic acids and their derivatives. Id. at 5:4–6. Particularly
preferred alkyl-substituted celluloses are hydroxyethylcellulose and HPMC.
Ex. 1003, 5:17–18. A particularly preferred polyalkylene oxide is PEO. Id.
at 5:22–23.
The Shell 1998 Publication further discloses that in terms of their
viscosities, one class of preferred alkyl-substituted celluloses includes those
whose viscosity is within the range of about 100 to about 110,000 centipoise
as a 2% aqueous solution at 20°C, while another class includes those whose
viscosity is within the range of about 1,000 to about 4,000 centipoise as a
1% aqueous solution at 20°C. Id. at 5:13–16. For PEO, the Shell 1998
Publication teaches that a preferred viscosity range is about 50 to about
2,000,000 centipoise for a 2% aqueous solution at 20°C. Id. at 5:26–28.
The Shell 1998 Publication teaches that the water-swellable polymers
it discloses can be used individually or in combination with each other. Id.
at 6:32. According to the Shell 1998 Publication, “[c]ertain combinations
IPR2014-00652
Patent 6,723,340 B2

11
will often provide a more controlled release of the drug than their
components when used individually.” Id. at 6:32–34. The Shell 1998
Publication gives examples of such combinations, including combining
cellulose-based polymers with gums, such as hydroxyethyl cellulose or
hydroxypropyl cellulose combined with xanthan gum, or combining PEO
with xanthan gum. Id. at 6:34–36.
The polymer mixture can then be impregnated or combined with a
drug and formed into particles, tablets, or retained in capsules. Id. at 7:3–4,
7:24–26. According to the Shell 1998 Publication, the disclosed invention
applies to drugs that are “freely soluble” in water, meaning that one part of
the drug dissolves in less than about ten parts water. Id. at 4:7–9. “The
matrix itself is solid prior to administration and, once administered, remains
undissolved in (i.e., uneroded by) the gastric fluid for a period of time
sufficient to permit a majority of the drug to be released . . . .” Id. at 3:3–4.
2. Analysis
a. The Shell 1998 Publication Teaches or Suggests All
the Recited Limitations of Independent Claim 1
Independent claim 1 requires a solid monolithic matrix made of PEO
and HPMC with a drug dispersed in the matrix. Ex. 1001, 11:60–12:9. The
claim characterizes PEO and HPMC by a specified viscosity and states that
the drug must be water soluble. Id. The claim further recites that the weight
ratio of the polymers in the matrix must cause the matrix to swell when the
tablet gets to the stomach, so the tablet is retained in the stomach. Id.
According to Petitioner, the Shell 1998 Publication identifies a small
number of preferred polymers, including “particularly preferred” polymers
PEO and HPMC, used to create a solid polymeric matrix in which a drug is
IPR2014-00652
Patent 6,723,340 B2

12
dispersed. Pet. 25. Petitioner explains that the Shell 1998 Publication
teaches the use of the polymers individually or in combination. Id.; see Ex.
1008 ¶ 83. For example, the Shell 1998 Publication discloses polymeric
matrices made from combinations of PEO and hydroxyethyl cellulose. Pet.
25 (citing Ex. 1003, 12:13–16, 13:27–30). The Shell 1998 Publication also
lists hydroxyethyl cellulose and HPMC as two “[p]articularly preferred
alkyl-substituted celluloses” that can be used in the polymeric matrices. Ex.
1003, 5:17–18. Petitioner supports its position with the declaration of Dr.
Clive Wilson, who testifies that based on the disclosure of the Shell 1998
Publication, it would have been obvious for a skilled artisan to use
combinations of HPMC and PEO polymers to achieve a gastric retentive
controlled-release dosage form as recited in challenged claim 1. Ex.
1008 ¶ 88. Petitioner, thus, concludes that the Shell 1998 Publication
teaches or at least suggests the combination of PEO and HPMC for
polymeric matrices and renders the challenged claims obvious. Pet. 28.
Patent Owner contests Petitioner’s conclusion that the Shell 1998
Publication teaches or suggests a matrix made from a combination of PEO
and HPMC as required by independent claim 1. PO Resp. 13. To the
contrary, Patent Owner contends the Shell 1998 Publication does not
disclose or contemplate a matrix comprising the combination of PEO and
HPMC. Id. at 14. Patent Owner specifically argues that (1) the
overwhelming majority of polymeric matrices taught by the Shell 1998
Publication are made of just one polymer, and (2) the combinations taught
by the Shell 1998 Publication all use xantham gum or hydroxyethyl cellulose
because these polymer combinations “provide a more controlled release of
the drug than their components when used individually.” PO Resp. 14
IPR2014-00652
Patent 6,723,340 B2

13
(citing Ex. 1003, 6:32–36, 12:13–16, 13:22–14:5). Patent Owner also
contends that the Shell 1998 Publication does not include PEO and HPMC
on a “short list” of polymers that could be combined to form a polymeric
matrix. Id. at 18. Rather, Patent Owner argues that PEO and HPMC are on
a “short list” to be used either independently or in combination with other
polymers (such as xantham gum or hydroxyethyl cellulose) that did not meet
certain performance criteria for controlled drug release. Id. According to
Patent Owner, HPMC is not interchangeable with xantham gum or
hydroxyethyl cellulose for the purposes of creating gastric retentive,
controlled release tablets, because, as shown in Figure 6 of the Shell 1998
Publication, PEO and xantham gun were beneficial in a mixture with
hydroxyethyl cellulose, whereas HPMC was not. Id. at 18–19 (citing Ex.
1003, Fig. 6); Ex. 2009 ¶ 70.
Patent Owner further contends that not only does the Shell 1998
Publication fail to disclose, suggest, or teach the exact combination of PEO
and HPMC, but based on the Shell 1998 Publication, a person of ordinary
skill in the art specifically would not have contemplated combining PEO and
HPMC. PO Resp. 16; Ex. 2009 ¶ 58. Patent Owner contends that PEO and
HPMC performed adequately on their own to control drug release, and there
was no indication that combining PEO and HPMC would improve on their
independent performance, or would have been “promising to try.” Id.
Patent Owner specifically argues that without first identifying a deficiency
in the performance of individual polymers (e.g., PEO and HPMC alone), a
person of ordinary skill in the art would not have combined them, and even
if a person of ordinary skill in the art would have combined the polymers,
the behavior of the resultant mixture would not have been predictable. Id.
IPR2014-00652
Patent 6,723,340 B2

14
(citing Ex. 2009 ¶¶ 59–63). Patent Owner relies on the declaration of Dr.
Hopfenberg to support its position. Dr. Hopfenberg testifies that:
[C]ombining polymers introduces uncertainty related to the
structure and properties of the combination of individual
polymers comprising the combination. These structural
variations can significantly affect the properties that are critical
for a gastric-retentive controlled release form, including
swelling, drug release, mechanical integrity, and the tendency
to undergo long term degradation of the matrix of the dosage
form subsequent to the designed release.

Ex. 2009 ¶ 59.

The results set forth in Figure 6 of the Shell 1998 [publication]
reveal that, with respect to drug retention in the dosage form
after immersion for one hour, the behavior of the mixtures was
unpredictable based on the behavior of the corresponding
homopolymers . . . [t]he HEC/PEO and HEC/XG mixtures
[used in the immersion experiment] showed significant
improvement over HEC alone, yet the HEC/HPMC mixture,
similar to HEC alone, failed to retain at least 40% of the drug
after one hour. The dramatically different effect on drug
retention following immersion resulting from forming an HEC
combination with HPMC, as opposed to forming an HEC
combination with PEO or XG, could not have been predicted.
Id. ¶ 63.

Thus, Patent Owner concludes that given the unpredictability of mixing two
different polymers, a person of ordinary skill in the art would not set out to
do so, absent a compelling motivation, and the Shell 1998 Publication
provides no such motivation. PO Resp. 17–18 (citing Ex. 2009 ¶ 64).
We do not agree with Patent Owner, because an obviousness analysis
“need not seek out precise teachings directed to the specific subject matter of
the challenged claim, for a court can take account of the inferences and
IPR2014-00652
Patent 6,723,340 B2

15
creative steps that a person of ordinary skill in the art would employ.” KSR,
550 U.S. at 418; see In re Translogic Tech., Inc., 504 F.3d. at 1259. A
combination would have been obvious under § 103 if “there are a finite
number of identified, predictable solutions” to a known problem and when a
path has been identified that “leads to the anticipated success, it is likely the
product not of innovation but of ordinary skill and common sense.” KSR,
550 U.S. at 418. The Court of Appeals for the Federal Circuit has elaborated
that the identified path must “present a finite (and small in the context of the
art) number of options easily traversed to show obviousness.” Ortho–
McNeil Pharm., Inc. v. Mylan Labs., Inc., 520 F.3d 1358, 1364 (Fed.Cir.
2008).
Although the Shell 1998 Publication does not disclose a polymeric
matrix made from a combination of PEO and HPMC, it does disclose a short
list of polymers to be used individually in producing a solid matrix for
controlled drug release, of which HPMC (Ex. 1003, 5:17–18) and PEO (id.
at 5:22–23) are particularly preferred polymers. The Shell 1998 Publication
also teaches that polymers can be combined to form a polymeric matrix. Id.
at 6:32–34. The Shell 1998 Publication does not limit which polymers could
be combined or suggest that certain polymers would not function properly in
a combination matrix. Id.; see In re Susi, 440 F.2d 442, 445 (CCPA 1971)
(affirming obviousness rejection where the disclosure of the prior art was
“huge, but it undeniably include[d] at least some of the compounds recited in
appellant’s generic claims and it is of a class of chemicals to be used for the
same purpose as appellant’s additives”). Furthermore, we credit the
testimony of Dr. Wilson, who stated that “as of October 2001, PEO and
HPMC were widely known polymers in the art for use in controlled release
IPR2014-00652
Patent 6,723,340 B2

16
drug delivery systems” and “the Shell 1998 Publication identifies only a
limited number of particularly preferred polymers, including PEO and
HPMC.” Ex. 1044 ¶ 28. Those facts support a conclusion that one would
have understood that the Shell 1998 Publication “teaches that these polymers
can be used in combination.” Id. Thus, given the teachings in the Shell
1998 Publication, we determine that there were a finite number of identified,
predictable polymers that could be used individually or in combination to
create a solid matrix for controlled drug release and we further determine
that the combination of PEO and HPMC, identified by the Shell 1998
Publication as particularly preferred polymers, would have been obvious to
one of ordinary skill in the art at the time of the ’340 patent. KSR, 550 U.S.
at 421 (describing that a person of ordinary skill possesses “ordinary
creativity, [and is] not an automaton”).
Patent Owner, however, argues that even if a person of skill in the art
would have contemplated a combination of PEO and HPMC in light of the
Shell 1998 publication, there would not have been a reasonable expectation
of success because it could not be predicted whether the disclosed polymer
mixtures would have worked. PO Resp. 21 (citing Ex. 2009 ¶ 63). Yet,
obviousness does not require absolute predictability. Allergan, Inc. v.
Apotex, Inc., 754 F.3d 952, 965 (Fed. Cir. 2014); In re O’Farrell, 853 F.2d
894, 903 (Fed.Cir.1988). What does matter is whether the prior art gives
direction as to what parameters are critical and which of many possible
choices may be successful. Allergan, 754 F.3d at 965. While success in
employing the disclosed polymers to form a solid matrix for controlled drug
release may not have been guaranteed, we are satisfied that explicitly
identifying PEO and HPMC as particularly preferred polymers sufficiently
IPR2014-00652
Patent 6,723,340 B2

17
provided guidance as to what parameters and polymers would lead to a
reasonable expectation of success.
Therefore, we determine that the Shell 1998 Publication at least
suggests a polymeric matrix made from a combination of PEO and HPMC
and, given the Shell 1998 Publication’s teachings, we find that a person of
ordinary skill in the art would have been able to make and use the claimed
invention without anything more than routine experimentation.
Accordingly, we hold that Petitioner has shown by a preponderance of the
evidence that independent claim 1 is unpatentable under 35 U.S.C. § 103(a)
for obviousness in view of the Shell 1998 Publication.
b. The Shell 1998 Publication Teaches or Suggests the
Recited Limitations of Dependent Claims 3–5 and 11–
13
Petitioner contends dependent claims 3–5 and 10–13 are unpatentable
under 35 U.S.C. § 103(a) for obviousness over the Shell 1998 Publication.
Pet. 27–28. Patent Owner contests Petitioner’s position, arguing that the
challenged dependent claims share the same material requirement of a
PEO/HPMC combination as independent claim 1, and therefore, for the
same reasons that claim 1 is not obvious over the Shell 1998 Publication, the
dependent claims also are not obvious over the Shell 1998 Publication. PO
Resp. 24. We agree with Petitioner’s position, as supported by the testimony
of Dr. Wilson, that the Shell 1998 Publication teaches the HPMC and PEO
molecular weight and viscosities required by dependent claims 3 and 4 (Ex.
1003, 4:33–5:1, 5:13–15, 5:28–30), as well as the drug water solubility
required by dependent claim 5 (id. at 4:9–12) and the proportions of the
dosage form made up by the combination of PEO and HPMC required by
dependent claims 11–13 (id. at Example 1, 8). See Ex. 1008 ¶¶ 82, 91, 125,
IPR2014-00652
Patent 6,723,340 B2

18
130, 131, 135, 141, 144, 147. Accordingly, we hold that Petitioner has
shown by a preponderance of the evidence that dependent claims 3–5 and
11–13 are unpatentable under 35 U.S.C. § 103(a) for obviousness in view of
the Shell 1998 Publication.
c. The Shell 1998 Publication Fails to Teach or Suggest
the Recited Limitations of Dependent Claim 10
Petitioner contends dependent claim 10 is unpatentable under 35
U.S.C. § 103(a) for obviousness over the Shell 1998 Publication. Pet. 27–
28. Patent Owner contests Petitioner’s position, arguing that the challenged
dependent claim 10 shares the same material requirement of a PEO/HPMC
combination as independent claim 1, and therefore, for the same reasons that
claim 1 is not obvious over the Shell 1998 Publication, claim 10 also is not
obvious over the Shell 1998 publication. PO Resp. 24.
While we agree with Petitioner that the Shell 1998 Publication teaches
or suggests the limitations of claims 1, 3–5, and 11–13, we are not satisfied
that Petitioner has shown by a preponderance of the evidence that the Shell
1998 Publication teaches or suggests the PEO:HPMC weight ratio set forth
in dependent claim 10. The testimony of Petitioner’s declarant, Dr. Wilson,
merely provides that the Shell 1998 Publication “disclose[s] a controlled-
release dosage form dispersed in a water-swellable polymeric matrix, and
that the polymers of the matrix, including PEO and HPMC, can be used
individually or in combination.” See Ex. 1008 ¶¶ 138, 140. Neither
Petitioner nor Dr. Wilson provide an explanation of how the Shell 1998
Publication renders the specific PEO:HPMC weight ratios set forth in
dependent claim 10 obvious. A determination of obviousness cannot be
sustained by mere conclusory statements; instead, there must be some
IPR2014-00652
Patent 6,723,340 B2

19
articulated reasoning with some rational underpinning to support the legal
conclusion of obviousness. KSR, 550 U.S. at 418; In re Kahn, 441 F.3d 977,
988 (Fed. Cir. 2006).
Furthermore, we must be careful not to allow hindsight reconstruction
of references to reach the claimed invention without any explanation as to
how or why the reference would produce the claimed invention. Kinetic
Concepts, Inc. v. Smith & Nephew, Inc., 688 F.3d 1342, 1368 (Fed. Cir.
2012) (quoting Innogenetics, N.V. v. Abbott Labs., 512 F.3d 1363, 1374 n.3
(Fed. Cir. 2008)); see also KSR, 550 U.S. at 421 (“A factfinder should be
aware, of course, of the distortion caused by hindsight bias and must be
cautious of arguments reliant upon ex post reasoning.”).
Accordingly, we hold that Petitioner has not shown by a
preponderance of the evidence that dependent claim 10 is unpatentable
under 35 U.S.C. § 103(a) for obviousness in view of the Shell 1998
Publication.
E. Alleged Obviousness of Claims 1, 3–5, and 10–13 in View of the
Shell 1998 Publication and Papadimitriou
Petitioner contends claims 1, 3–5, and 10–13 of the ’340 patent are
unpatentable under 35 U.S.C. § 103 in view of the Shell 1998 Publication
and Papadimitriou. Pet. 29–32. Patent Owner disputes Petitioner’s position,
arguing that that one of skill in the art would not have combined the Shell
1998 Publication and Papadimitriou. PO Resp. 24–34. We have reviewed
the Petition, the Patent Owner Response, and Petitioner’s Reply, as well as
the relevant evidence discussed in those papers. For reasons that follow, we
determine that Petitioner has shown by a preponderance of the evidence that
IPR2014-00652
Patent 6,723,340 B2

20
the challenged claims would have been obvious in view of the Shell 1998
Publication and Papadimitriou.
1. Overview of Papadimitriou
Papadimitriou discloses a sustained drug delivery system achieved
“by the use of hydrophilic polymer excipients, which swell in the presence
of water.” Ex. 1007, 232. Papadimitriou examines the percolation threshold
for polymeric matrices and the impact of varying the concentration of
hydrophilic polymer excipients in the matrices on drug release rates from
lattice-type matrices. Id. at 232–33. Papadimitriou teaches the use of
HPMC and PEO as hydrophilic water-swellable polymers, alone or in
combination. Id. at 233, Fig. 1. The polymers are compressed into tablets
that have a diameter of 9 mm and a height of 8mm. Id. As shown in Figure
1 of Papadimitriou, reproduced below, a polymer matrix containing PEO
and HPMC swelled by at least 40% of its original size within 30 minutes.

Figure 1 of Papadimitriou illustrates increases in weight (%) as a function of
time for matrices composed of HPMC and/or PEO.
IPR2014-00652
Patent 6,723,340 B2

21
Based on the results indicated in Figure 1, Papadimitriou states “all the
tablets were observed to swell significantly, as indicated by the large weight
increase.” Ex. 1007, 233.
Papadimitriou discloses PEO with a viscosity average molecular
weight of from about 2,000,000 to 10,000,000 daltons. Id. at 233.
Papadimitriou also discloses HPMC (i.e., Methocel K100M) with a viscosity
in a range of approximately 4,000–200,000 centipoise, measured as a 2%
solution in water. Id. at 233. Papadimitriou further discloses combinations
of HPMC and PEO with ratios ranging from 100% HPMC:0% PEO to
0%HPMC:100%PEO. Id. at 233.
2. Overview of the Shell 1998 Publication
The disclosure of the Shell 1998 Publication is discussed in detail
above in Section II.D.1.
3. Analysis
a. The Shell 1998 Publication and Papadimitriou Teach
or Suggest All the Recited Limitations of Independent
Claim 1
As discussed previously, independent claim 1 requires a solid
monolithic matrix made of PEO and HPMC with a drug dispersed in the
matrix. Ex. 1001, 11:60–12:9. Petitioner contends the Shell 1998
Publication in combination with Papadimitriou, as summarized above,
teaches each limitation of claim 1. Pet. 28–31. Specifically, Petitioner
argues that (1) the Shell 1998 Publication identifies a small number of
preferred polymers, including “particularly preferred” polymers PEO and
HPMC, that can be used individually or in combination to create a solid
polymeric matrix in which a drug is dispersed, and (2) Papadimitriou
likewise discloses a sustained drug delivery system achieved “by the use of
IPR2014-00652
Patent 6,723,340 B2

22
hydrophilic polymer excipients, which swell in the presence of water” and
expressly teaches the use of HPMC and PEO as hydrophilic, water-swellable
matrix polymers, alone or in combination. Id.; see Ex. 1008 ¶ 92 (citing Ex.
1003, 6:32; Ex. 1007, 232), ¶ 93 (citing Ex. 1007, 232, Fig. 1). Petitioner
further notes that Papadimitriou specifically discloses Methocel K100M, a
commercially available HPMC having a viscosity of 100,000 centipoise.
Pet. 29; Ex. 1008 ¶¶ 93, 101.
According to Petitioner, a person of ordinary skill in the art would
have been led to combine the teachings of the Shell 1998 Publication with
Papadimitriou, because the disclosures share the common goal of releasing a
drug in a controlled or sustained manner by using a swellable polymeric
matrix. Pet. 30–31; see Ex. 1008 ¶ 94. Petitioner supports its position with
the declaration of Dr. Wilson, who testifies that a skilled artisan “reading the
Shell 1998 Publication would look to Papadimitriou for further examples of
polymer matrices that would be compatible with the teachings of the Shell
1998 Publication.” Ex. 1008 ¶ 94. Petitioner then concludes that the
polymer matrix of Papadimitriou comprising a combination of HPMC and
PEO can be used in the drug dosage form of the Shell 1998 Publication. Pet.
31; see Ex. 1008 ¶ 94.
Patent Owner disagrees with Petitioner’s contention that one of
ordinary skill in the art would look to combine the teachings of the Shell
1998 Publication and Papadimitriou. PO Resp. 24. First, Patent Owner
argues that Papadimitriou does not disclose, teach, or suggest any benefit of
the PEO/HPMC combination to any dosage form, let alone a gastric
retentive one, but instead focuses on the unpredictable polymer-to-polymer
interactions in such mixtures in order to underscore the complexities and
IPR2014-00652
Patent 6,723,340 B2

23
pitfalls of such polymer mixtures. Id. at 26; Ex. 2009 ¶ 74. Patent Owner
then argues “[Petitioner] concedes that Papadimitriou does not teach or
suggest gastric retentive drug dosage forms at all” because Petitioner’s claim
charts do not cite to Papadimitriou in relation to gastric retention. PO Resp.
28 (citing Pet. 20–21).
Second, Patent Owner argues that a person of ordinary skill in the art
would not have combined Papadimitriou with the Shell 1998 Publication,
because Papadimitriou is not related to gastric retention, which was an
essential component of the problem solved by the ’340 patent. Id. at 28.
Patent Owner supports its argument that Papadimitriou is not directed to a
gastric retentive dosage form with the fact that the swelling experiments in
Papadimitriou were conducted at a neutral pH of 7.4, instead of an acidic pH
similar to that of gastric fluid. Id. at 28–29 (citing Ex. 1007, 233); Ex. 2009
¶ 79. Patent Owner then argues that Papadimitriou’s experiments are
deficient because Papadimitriou did not present any drug release profiles,
and in fact, did not even include drug in any experiment. Id. at 30 (citing
Ex. 1007, 233 (“In this work, the degree of swelling of combinations of the
two excipients alone (i.e. without drug or other excipients) is considered.”))
(emphasis added); Ex. 2009 ¶ 80. According to Patent Owner, the presence
of drug would further impact how the polymers swelled. PO Resp. 30.
Patent Owner further argues that the assays reported in Papadimitriou were
carried out in phosphate buffer, which was known to be problematic for PEO
because it leads to phase separation. Id. (citing Ex. 2009 ¶ 81; Ex. 2015
¶ 29). Patent Owner relies on the testimony of Dr. Hopfenberg, whose
testimony reiterates Patent Owner’s contentions regarding the teachings in
Papadimitriou. Ex. 2009 ¶¶ 74–87. Based on the postulated problems with
IPR2014-00652
Patent 6,723,340 B2

24
the experimental designs disclosed in Papadimitriou, Patent Owner asserts
that a skill artisan would not rely on Papadimitriou in the creation of a
controlled release dosage form, let alone a gastric retentive one. Id. at 30.
Lastly, Patent Owner argues that the combination of the Shell 1998
Publication and Papadimitriou would not have provided a person of ordinary
skill in the art with a reasonable expectation of success in practicing the ’340
patent claims. Id. at 31. According to Patent Owner, (i) a person of ordinary
skill in the art would not have found the teachings of the Shell 1998
Publication and Papadimitriou compatible or directed to similar issues (id. at
31), and (ii) the unpredictable interactions of polymers as disclosed by
Papadimitriou indicates that a person of ordinary skill “could not predict
whether the disclosed xantham-based and HEC-based polymer combinations
would work, as reflected by ‘failed’ combinations such as HEC/HPMC” (id.
at 32–33 (citing Ex. 2009 ¶ 63)). Thus, Patent Owner concludes that a
combination of the Shell 1998 Publication and Papadimitriou is based on
impermissible hindsight because a skilled artisan would not have combined
the teachings of the two references. Id. at 33.
Despite Patent Owner’s arguments, we agree with Petitioner that
challenged claims 1, 3–5, and 10–13 would have been obvious over the
Shell 1998 Publication and Papadimitriou. Specifically, we find that a
skilled artisan would look to the teachings of Papadimitriou in combination
with the Shell 1998 Publication’s disclosure in attempts to solve the problem
of releasing a drug in a controlled or sustained manner by using a
combination of PEO and HPMC, both of which are swellable hydrophilic
polymers. This finding is based on the fact that Papadimitriou’s disclosure
is directed specifically to “sustained drug delivery . . . by the use of
IPR2014-00652
Patent 6,723,340 B2

25
hydrophilic polymeric excipients” (Ex. 1007, 232), while the Shell 1998
Publication is directed to sustained release unit dosage forms incorporated
into polymeric matrices made of hydrophilic polymers (Ex. 1003, Abstract).
See id. at 2:30–32, 3:8–11, 6:32–34; Ex. 1007, Abstract, 233; see also Ex.
1008 ¶ 92 (“[T]he Shell 1998 patent publication discloses that the water-
swellable polymer matrix in which the drug is dispersed may be formed of
an individual polymer or a combination of polymers (Exh. 1003, 6:32) . . .
Papadimitriou expressly teaches the use of HPMC and PEO as hydrophilic,
water-swellable matrix polymers, alone or in combination. (Exh. 1007, p.
233, Fig. 1).”) Therefore, contrary to Patent Owner’s statements, the
references are directed to similar issues and disclose PEO and HPMC as
swellable hydrophilic polymers. Accordingly, we hold that a skilled artisan
at the time of the invention would have considered the teachings of
Papadimitriou compatible with the teachings of the Shell 1998 Publication,
and would apply the disclosures in combination.
We also are not persuaded by Patent Owner’s arguments, as they
narrowly focus on small differences between Papadimitriou and the Shell
1998 Publication and fail to consider the collective teachings of
Papadimitriou and the Shell 1998 Publication from the perspective of one of
ordinary skill in the art. See KSR, 550 U.S. at 420 (“[F]amiliar items may
have obvious uses beyond their primary purpose, and in many cases a person
of ordinary skill will be able to fit the teachings of multiple patents together
like pieces of a puzzle.”) The fact that Papadimitriou uses PEO and HPMC,
which are called out specifically in the Shell 1998 Publication as particularly
preferred polymers to use, weighs in favor of finding that a person of
ordinary skill in the art would “fit the teachings” of Papadimitriou and the
IPR2014-00652
Patent 6,723,340 B2

26
Shell 1998 Publication together to render the challenged claims obvious.
Additionally, the arguments presented by Patent Owner appear to attack
Papadimitriou individually, rather than in combination with the Shell 1998
Publication. See PO Resp. 26–30. Nonobviousness cannot be established
by attacking the references individually when a challenge is predicated upon
a combination of prior art disclosures. See In re Merck & Co., Inc., 800 F.2d
1091, 1097 (Fed. Cir. 1986). In attacking Papadimitriou individually, Patent
Owner fails to address Petitioner’s actual challenges or, therefore, establish
an insufficiency in the combined teachings of the references.
Furthermore, we are not persuaded by Patent Owner’s arguments that
the combination of the Shell 1998 Publication and Papadimitriou would not
have provided a person of ordinary skill in the art with a reasonable
expectation of success in practicing the ’340 patent claims because the
nature of polymer mixtures is unpredictable. The case law is clear that
obviousness cannot be avoided simply by showing some degree of
unpredictability in the art, as long as there was a reasonable probability of
success. See Pfizer, Inc. v. Apotex, 480 F.3d 1348, 1369 (Fed. Cir. 2007);
(holding that “a skilled artisan would have had a reasonable expectation of
success with the besylate salt form of amlodipine at the time the invention
was made”); In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985) (“Although
[the inventor] declared that it cannot be predicted how any candidate will
work in a detergent composition, but that it must be tested, this does not
overcome [the prior art’s] teaching that hydrated zeolites will work.”).
This is not a case where the prior art merely teaches to pursue a
“general approach that seemed to be a promising field of experimentation”
or “gave only general guidance as to the particular form of the claimed
IPR2014-00652
Patent 6,723,340 B2

27
invention or how to achieve it.” O’Farrell, 853 F.2d at 903 (“Obviousness
does not require absolute predictability of success . . . [A]ll that is required is
a reasonable expectation of success.”); Medichem, S.A. v. Rolabo, S.L., 437
F.3d 1157, 1165 (Fed.Cir.2006) (“While the definition of ‘reasonable
expectation’ is somewhat vague, our case law makes clear that it does not
require a certainty of success.”) (internal citations omitted). Although
success in employing the disclosed polymers to form a solid matrix for
controlled drug release may not have been guaranteed, we are satisfied that
the Shell 1998 Publication in view of Papadimitriou sufficiently provided
guidance as to what parameters and polymers would lead to a reasonable
expectation of success by explicitly identifying PEO and HPMC as
particularly preferred polymers.
Accordingly, we hold that Petitioner has shown by a preponderance of
the evidence that independent claim 1 is unpatentable under 35 U.S.C.
§ 103(a) for obviousness in view of the Shell 1998 Publication and
Papadimitriou.
b. The Shell 1998 Publication and Papadimitriou Teach
or Suggest the Recited Limitations of Dependent
Claims 3–5 and 10–13
Petitioner contends dependent claims 3–5 and 10–13are unpatentable
under 35 U.S.C. § 103(a) for obviousness over the Shell 1998 Publication
and Papadimitriou. Pet. 31–32. Patent Owner contests Petitioner’s position,
arguing that the challenged dependent claims share the same material
requirement of PEO/HPMC combinations as independent claim 1, and
therefore, for the same reasons that claim 1 is not obvious over the Shell
1998 Publication and Papadimitriou, the dependent claims also are not
IPR2014-00652
Patent 6,723,340 B2

28
obvious over the Shell 1998 Publication and Papadimitriou. PO Resp. 34.
For reasons stated above, we find that position unpersuasive.
We agree with Petitioner’s further position, as supported by the
testimony of Dr. Wilson, that the Shell 1998 Publication and Papadimitriou
teach (a) the HPMC and PEO molecular weight and viscosities required by
dependent claims 3 and 4 (Ex. 1003, 4:33–5:1, 5:13–15, 5:28–30), (b) the
drug water solubility required by dependent claim 5 (id. at 4:9–12), (c) the
weight ratio of PEO to HPMC as required by dependent claim 10 (Ex. 1007,
233), and (d) the proportions of the dosage form made up by the
combination of PEO and HPMC required by dependent claims 11–13 (Ex.
1003, Example 1, 8). See Ex. 1008 ¶¶ 91, 92, 127, 128, 133–137, 139, 141–
149. Accordingly, we hold that Petitioner has shown by a preponderance of
the evidence that dependent claims 3–5 and 10–13 are unpatentable under 35
U.S.C. § 103(a) for obviousness in view of the Shell 1998 Publication.
F. Alleged Obviousness of Claims 1, 3–5, and 10–13 in View of
Edgren and Papadimitriou
Petitioner contends claims 1, 3–5, and 10–13 of the ’340 patent are
unpatentable under 35 U.S.C. § 103 in view of Edgren and Papadimitriou.
Pet. 39–42. Patent Owner disputes Petitioner’s position, arguing that one of
skill in the art would not have had reason to combine Edgren and
Papadimitriou. PO Resp. 34–42. We have reviewed the Petition, the Patent
Owner Response, and Petitioner’s Reply, as well as the relevant evidence
discussed in those papers. For reasons that follow, we determine that
Petitioner has not shown by a preponderance of the evidence that the
challenged claims are unpatentable as obvious over Edgren and
Papadimitriou.
IPR2014-00652
Patent 6,723,340 B2

29
1. Overview of Edgren
Edgren describes a controlled-release dosage form for delivering a
drug in the gastrointestinal tract comprising a beneficial drug and at least
two different cellulose ethers (i.e., a polymer matrix) that swell when
hydrated. Ex. 1006, 1:12–13, 2:37–52; 3:17, 11:23–28. Edgren further
discloses that its polymeric matrices are composed of a low number average
molecular weight HPMC and a high number average molecular weight
HPMC. Id. at Abstract, 5:10–26, 11:23–28. The drugs disclosed in Edgren
include those that are very soluble, such as captopril and ranitidine. Id. at
2:53–56, 2:61–68, 5:27–67, 8:47; 9:1–2. Edgren describes a drug dosage
form comprising at least thirty weight percent of HPMC polymers and up to
seventy weight percent of a soluble drug. Id. at 1:17–19, 1:30–32, 3:8–10.
According to Edgren, the drug/HPMC mixture can be fed into a hopper of a
compression machine, where about two tons of pressure is applied to
compress the composition together into a dosage form. Id. at 7:27–31.
Edgren teaches that the disclosed HPMC polymers make “available a
drug delivery matrix suitable for retention in the stomach for gastric
retention over the drug releasing life time of the dosage system.” Id. at
10:65–68. Edgren further teaches that the HPMC polymers swell
extensively when hydrated and reduce irritation of mucosal tissue by the
drug because there is less direct drug contact with the tissue. Id. at 11:23–
28.
2. Overview of Papadimitriou
The disclosure of Papadimitriou is discussed in detail above in Section
II.E.2.
IPR2014-00652
Patent 6,723,340 B2

30
3. Analysis
Petitioner contends Edgren, as summarized above, in combination
with Papadimitriou teaches or suggests each limitation of claims 1–5 and
10–13 of the ’340 patent. Pet. 39–42. Petitioner specifically contends that
Edgren teaches the use of polymeric ethers in combination and does not
teach away from using PEO with HPMC. Reply 8. Petitioner supports its
position with a declaration of Dr. Wilson, who testifies that the “Background
of the Invention” section of Edgren describes disadvantages of prior art
formulations that used HPMC with other cellulosic ethers, however, none of
the prior art cited in Edgren used PEO. Ex. 1044 ¶ 63. Dr. Wilson,
therefore, opines that Edgren cannot be considered as teaching away from
using polymers, such as PEO and HPMC, in combination. Id. ¶ 64.
Petitioner also contends that a person of ordinary skill in the art would
have been led to combine the teachings of Edgren with Papadimitriou,
because the disclosures share the common goal of releasing a drug in a
controlled or sustained manner by using a swellable polymeric matrix. Id. at
40–41; see Ex. 1008 ¶¶ 115–116. According to Petitioner, a skilled artisan
reading Edgren would look to Papadimitriou for further examples of
polymer matrices that would be compatible with the teachings of Edgren.
Petitioner then contends that one of the goals of Edgren was to provide
greater mechanical integrity than the dosage forms of the prior art, and PEO,
as disclosed in Papadimitriou, was a readily available polymer with high
swelling potential that was known to increase mechanical integrity. Reply 9
(citing Ex. 1043 ¶ 65; Ex. 1006, 1:27–44, 3:1–7, 11:3–7; Ex. 2023, 145:4–
149:2). Petitioner concludes that because it was known that polymers could
be combined to provide better controlled release (see, e.g., Ex. 1003), it
IPR2014-00652
Patent 6,723,340 B2

31
would have been obvious to a skilled artisan that the polymer matrix of
Papadimitriou, comprising a combination of HPMC and PEO, could have
been used in the drug dosage form of Edgren. Pet. 41; Reply 9 (citing Ex.
1043 ¶ 65).
Patent Owner disagrees with Petitioner’s contention, arguing the
claim would not have been obvious in view of the combination of Edgren
and Papadimitriou, for several reasons. PO Resp. 34–41. First, Patent
Owner argues that a skilled artisan would not have combined Edgren with
Papadimitriou because Edgren teaches away from the claimed PEO/HPMC
combination. Id. at 35. According to Patent Owner, Edgren specifically
discourages combining HPMC with polymeric ethers (of which PEO is a
member). Id. Second, Patent Owner argues there is no reason why a skilled
artisan would have thought to combine the elements of Edgren and
Papadimitriou, because (i) Edgren is directed to combining two forms of
HPMC, (ii) Edgren does not disclose PEO, (iii) PEO and HPMCs are not
interchangeable, (iv) Papadimitriou – and its disclosure of a PEO/HPMC
combination – does not apply to gastric retentive dosage form, and (v)
reading Edgren and Papadimitriou together would not provide a skilled
artisan with a reasonable expectation that the unique PEO/HPMC
combination of the’340 patent would work for the intended purpose of
providing gastric retention and controlled drug release. Id. at 37–39; see Ex.
2009 ¶¶ 92–93.
On the record developed at trial, we are not persuaded that Petitioner
has shown by a preponderance of the evidence that a person of ordinary skill
in the art would have had a reason to combine the references with a
reasonable expectation of success. Although the references may have
IPR2014-00652
Patent 6,723,340 B2

32
interrelated teachings because they both are directed to polymers, Petitioner
has not explained persuasively how or why a person of ordinary skill in the
art would have exchanged one of the HPMCs in the Edgren formulation with
PEO in the formulation of Papadimitriou.
Edgren specifically discloses using “at least two cellulose ethers that
function together for enhancing the pharmaco-release kinetics of the dosage
form” and using a “cellulose ether formulation [of high molecular weight
HPMC and low molecular weight HPMC that] operate[s] as a unit in a
moving fluid for controlling the rate of release of a beneficial drug from the
dosage form.” Ex. 1006, 2:33–45. Despite this disclosure, Petitioner argues
that a skilled artisan would have used PEO in the Edgren formulation simply
because “PEO was a readily available polymer with high swelling potential
that was known to increase mechanical integrity.” See Reply 9; Ex. 1043
¶ 65. Petitioner provides insufficient evidence that a person of skill in the
art would have found PEO (a non-cellulose ether) to be interchangeable with
low molecular weight HPMC (a cellulose ether) or that PEO would have
been able to act as a unit with high molecular weight HPMC as described in
Edgren. In fact, at deposition, Petitioner’s declarant, Dr. Wilson, testified
that PEOs and low molecular weight HPMCs are not interchangeable.
Q. Is it your position that all of the Polyoxes that make up the
class of Polyoxes and all of the low molecular weight
HPMCs that make up that class are interchangeable in terms
of their ability to absorb water?
A. No.
Q. They are not interchangeable?
A. They are not interchangeable.
You would get a different characteristic
but then you would blend backwards and
IPR2014-00652
Patent 6,723,340 B2

33
forwards to get the required uptake of
water you are seeking.
Q. So there are differences amongst the various Polyox and
low molecular weight HPMCs in terms of their ability to
absorb water, correct?
A. Yes, there is, yes.
Q. And there are, likewise, differences in terms of their ability
to swell?
A. Yes.
Q. And in terms of their ability to erode, correct?
A. That’s true.
Ex. 2023, 279:21–280:21.
Given this testimony, we find that Petitioner’s argument is fraught
with hindsight bias. See KSR, 550 U.S. at 418 (“A patent composed of
several elements is not proved obvious by merely demonstrating that each of
its elements was, independently, known in the prior art.”); Kinetic Concepts,
Inc. v. Smith & Nephew, Inc., 688 F.3d 1342, 1368–69 (Fed. Cir. 2012)
(“[Smith & Nephew] never offered evidence articulating why a person
having ordinary skill in the art would combine the primary references to
obtain the disclosed inventions.”); Innogenetics, N.V. v. Abbott Labs., 512
F.3d 1363, 1373–74 (Fed. Cir. 2008) (“We must still be careful not to allow
hindsight reconstruction of references to reach the claimed invention without
any explanation as to how or why the references would be combined to
produce the claimed invention.”). In the absence of PEO and low molecular
weight HPMC being readily interchangeable, Petitioner needed to explain
what would have led a person of ordinary skill in the art at the time of the
invention to replace low molecular weight HPMC in the Edgren formulation
with PEO. Petitioner failed to provide such an explanation.
IPR2014-00652
Patent 6,723,340 B2

34
Petitioner must demonstrate obviousness by a preponderance of the
evidence. See Yamaha Int’l Corp. v. Hoshino Gakki Co., 840 F.2d 1572,
1580 n.11 (Fed. Cir. 1988) (stating that the ultimate burden of persuasion [to
establish a fact by a preponderance of the evidence] is only critical in the
situation where the evidence is so evenly balanced that no preponderance
emerges. In that event, the party having the burden of persuasion
necessarily loses.). After considering the parties’ arguments and evidence,
however, we are not persuaded that Petitioner has made a sufficient showing
that a person of ordinary skill would have combined the teachings in the
manner contended by Petitioner. Accordingly, we hold that Petitioner has
not shown by a preponderance of the evidence that independent claim 1 is
unpatentable under 35 U.S.C. § 103(a) for obviousness in view of Edgren
and Papadimitriou. For the same reasons, we are hold Petitioner has failed
to establish the unpatentability of dependent claims 3–5 and 10–13 by a
preponderance of the evidence.
G. Secondary Considerations of Non-Obviousness
Factual inquiries for an obviousness determination include secondary
considerations based on evaluation and crediting of objective evidence of
nonobviousness. See Graham, 383 U.S. at 17. Notwithstanding what the
teachings of the prior art would have suggested to one of ordinary skill in the
art at the time of the invention, the totality of the evidence submitted,
including objective evidence of nonobviousness, may lead to a conclusion
that the challenged claims would not have been obvious to one of ordinary
skill in the art. In re Piasecki, 745 F.2d 1468, 1471–72 (Fed. Cir. 1984).
Secondary considerations may include any of the following: long-felt but
unsolved needs, failure of others, unexpected results, commercial success,
IPR2014-00652
Patent 6,723,340 B2

35
copying, licensing, and praise. See Graham, 383 U.S. at 17; Leapfrog
Enters., Inc. v. Fisher-Price, Inc., 485 F.3d 1157, 1162 (Fed. Cir. 2007).
To be relevant, evidence of nonobviousness must be commensurate in
scope with the claimed invention. In re Kao, 639 F.3d 1057, 1068 (Fed. Cir.
2011) (citing In re Tiffin, 448 F.2d 791, 792 (CCPA 1971)); In re Hiniker
Co., 150 F.3d 1362, 1369 (Fed. Cir. 1998). In that regard, in order to be
accorded substantial weight, there must be a nexus between the merits of the
claimed invention and the evidence of secondary considerations. In re
GPAC Inc., 57 F.3d 1573, 1580 (Fed. Cir. 1995). “Nexus” is a legally and
factually sufficient connection between the objective evidence and the
claimed invention, such that the objective evidence should be considered in
determining nonobviousness. Demaco Corp. v. F. Von Langsdorff Licensing
Ltd., 851 F.2d 1387, 1392 (Fed. Cir. 1988). The burden of showing that
there is a nexus lies with the patent owner. Id.; see Paulsen, 30 F.3d at
1482. Here, Patent Owner argues that commercial success, licensing, long-
felt but unresolved need, unexpected results, and the length of time it took to
invent the challenged claims indicates that the claims would not have been
obvious to a person of ordinary skill in the art. PO Resp. 43–55.
1. Commercial Success
Patent Owner argues that it has successfully commercialized the
patented inventions in multiple drugs on the market. PO Resp. 49. As its
example, Patent Owner cites the drug Gralise® and its sales and market
share data. Id. at 50–51. As explained above, evidence of commercial
success is “only significant if there is a nexus between the claimed invention
and the commercial success.” Ormco Corp. v. Align Tech., Inc., 463 F.3d
1299, 1311–12 (Fed. Cir. 2006). To establish a nexus between a claimed
IPR2014-00652
Patent 6,723,340 B2

36
invention and the commercial success of a product, there must be “proof that
the sales [of the allegedly successful product] were a direct result of the
unique characteristics of the claimed invention—as opposed to other
economic and commercial factors unrelated to the quality of the patented
subject matter.” See In re GPAC, Inc., 57 F.3d 1573, 1580 (Fed. Cir. 1995)
(“For objective evidence to be accorded substantial weight, its proponent
must establish a nexus between the evidence and the merits of the claimed
invention.”); Demaco Corp. v. F. Von Langsdorff Licensing Ltd., 851 F.2d
1387, 1392 (Fed. Cir. 1988 ), cert. denied (1988) (“A prima facie case of
nexus is generally made out when the patentee shows both that there is
commercial success, and that the thing (product or method) that is
commercially successful is the invention disclosed and claimed in the
patent.”); Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 1539 (Fed. Cir.
1983) (holding that patent owner failed to show nexus between the merits of
the invention and the commercial success of a tubing product). On the
record before us, we are not persuaded that the evidence shows sufficiently a
nexus between any success of Patent Owner’s products and the invention
claimed in the ’340 patent.
Specifically, Patent Owner has not shown sufficiently in its Patent
Owner Response that Gralise® embodies the claims of the ’340 patent.
Instead, Patent Owner cites its declarant, Dr. Hopfenberg, and claim charts,
stating only that Dr. Hopfenberg “opines that there is a direct nexus between
the ‘340 patented technology and the Gralise® product.” PO Resp. 49
(citing Ex. 2009 ¶¶ 96–97). Patent Owner then states that “[b]y claim charts,
he finds that the Gralise® product embodies each and every limitation of the
claims of the ’340 Patent.” Id. at 49–50 (citing Ex. 2009 ¶ 97 (citing Ex.
IPR2014-00652
Patent 6,723,340 B2

37
2011, a 9-page claim chart)). We determine that merely citing to a claim
chart as support—without any explanation in the Patent Owner Response—
is insufficient to demonstrate a nexus and violates our rule against
incorporation by reference.6 See 37 C.F.R. § 42.6(a)(3) (“Arguments must
not be incorporated by reference from one document into another
document.”).
Accordingly, absent an adequate demonstration of nexus in the
Petition, we give little weight to Patent Owner’s argument that the alleged
commercial success of Gralise® is evidence that the claims are not obvious.
2. Licensing
Patent Owner also argues that its licensing program establishes that
the claims are not obvious. PO Resp. 51. Patent Owner asserts that it has
“entered into 10 different license agreements (two of them with one
licensee) since 2002 for the ‘340 patented technology (known as the
Acuform® technology).” Id. at 51–52. Patent Owner further asserts that its
licenses have “generated substantial upfront, milestone, and royalty
payments for [Patent Owner].” Id. at 52. Patent Owner concludes that
“[t]he fact that so many different third parties have acknowledged [Patent
Owner’s] patented technology and voluntarily made substantial payments
for licenses to the ‘340 patented technology is strong evidence that the
patented inventions were [not] obvious at their time.” Id. at 52–53.

6 We recognize the challenge of fully addressing the nexus issue within our
default page limits. We note, however, that Patent Owner did not request
additional pages for its Response or even attempt to address at least a single
claim in the Response.
IPR2014-00652
Patent 6,723,340 B2

38
We are not persuaded. As with evidence of commercial success,
“only little weight can be attributed to such evidence if the patentee does not
demonstrate a nexus between the merits of the invention and the licenses of
record.” In re GPAC Inc., 57 F.3d 1573, 1580 (Fed. Cir. 1995) (citation
omitted). Moreover, our reviewing court has held that “without a showing
of a nexus, ‘the mere existence of . . . licenses is insufficient to overcome the
conclusion of obviousness.’” In re Antor Media Corp., 689 F.3d 1282, 1293
(Fed. Cir. 2012) (quoting Iron Grip Barbell Co. v. USA Sports, Inc., 392
F.3d 1317, 1324 (Fed. Cir. 2004)).
Like the applicant in Antor Media, Patent Owner has done little more
than list the licenses and their respective sales revenue. See id. at 1293–94.
The cited testimony of Dr. Nicholson only details the revenues for each
license and does not establish whether the licensing program was successful
because of the merits of the claimed invention or for other economic
reasons, such as to avoid litigation or because of prior business relationships.
See Ex. 2014 ¶¶ 46, 77; see also Antor Media, 689 F.3d at 1294 (affirming
Board’s finding that evidence of existence of licenses was insufficient to
overcome prima facie case of obviousness).
Accordingly, we give little weight to Patent Owner’s argument that its
licensing program is evidence that the claims are not obvious.
3. Long-Felt but Unsolved Need
Patent Owner argues that Dr. Berner (inventor of the ’340 patent)
“provides credible information that there was a long-felt need for a once
daily, gastric-retentive, controlled-release dosage form to deliver highly
soluble drugs slowly, evenly, and reproducibly.” PO Resp. 53 (citing Ex.
2009 ¶¶ 98–99). Patent Owner also describes the use of the drugs
IPR2014-00652
Patent 6,723,340 B2

39
Metformin and gabapentin to reduce side-effects and increase patient-
compliance of prior art drugs. Id. at 53–54.
We are not persuaded. Patent Owner must show that any evidence of
long-felt need “demonstrates both that a demand existed for the patented
invention, and that others tried but failed to satisfy that demand.” In re
Cyclobenzaprine Hydrochloride Extended-Release Capsule Patent Litig.,
676 F.3d 1063, 1082 (Fed. Cir. 2012). Patent Owner’s argument is lacking
as to the latter element. That is, Patent Owner offers no evidence that others
tried and failed.
Accordingly, we give little weight to Patent Owner’s argument that
there was a long-felt but unmet need that overcomes Petitioner’s showing of
obviousness in this case.
4. Undue Experimentation and Unexpected Results
Patent Owner argues that the ’340 patent claims would not have been
obvious because it took the inventors one and a half years of extensive
experimentation to first recognize the “unexpectedly beneficial
performance” of PEO and HPMC for gastric retention and controlled drug
release. PO Resp. 44 (citing Ex. 2014 ¶ 24). According to Patent Owner,
“anything-but-‘routine experimentation’ was necessary” to conceive of the
claimed inventions in the ’340 Patent. Id. (citing Ex. 2014 ¶ 27). We find
this argument unpersuasive in light of Exhibits 2018 and 2019. As
Petitioner notes, PEO was used by scientists (working on a project for Patent
Owner) on the first day of the project, January 21, 1999 (Ex. 2018, 138), and
HPMC was suggested for use in the formulation on February 17, 1999 (id.
at. 180). We cannot pinpoint the exact date of invention for the ’340 patent
claims, because we are limited to the evidence of record. Given the record
IPR2014-00652
Patent 6,723,340 B2

40
that is available to us, we are not persuaded the inventors of the ’340 patent
took “approximately one and a half years of extensive experimentation” to
conceive the ’340 patent. The lengthy experiments performed in Exhibits
2018 and 2019 do not show lack of invention, because it appears Patent
Owner undertook that work to satisfy particular commercial requirements.
See CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333, 1340 (Fed. Cir. 2003)
(“In general, few patented inventions are an immediate commercial success.
Rather, most inventions require further development to achieve commercial
success.”).
Accordingly, we give little weight to Patent Owner’s argument that
the evidence of alleged unexpected results overcomes Petitioner’s showing
of obviousness in this case.
III. MOTIONS TO EXCLUDE EVIDENCE AND MOTION FOR
OBSERVATIONS REGARDING DEPOSITION TESTIMONY
Both parties filed motions to exclude evidence offered by the other
side. The party moving to exclude evidence bears the burden of proving that
it is entitled to the relief requested—namely, that the material sought to be
excluded is inadmissible under the Federal Rules of Evidence. See 37
C.F.R. §§ 42.20(c), 42.62(a). We address each party’s motion in turn.
A. Petitioner’s Motion to Exclude Evidence
Petitioner filed a Motion to Exclude Evidence seeking to exclude
Exhibits 2163 and 2164, which were introduced during the deposition of
Petitioner’s Declarant, Dr. Wilson. Paper 51 (“Mot.”). Even without
excluding this evidence, we have determined that Petitioner has established,
based on a preponderance of the evidence, the unpatentability of claims 1,
3–5, and 10–13 of the ’340 patent. Furthermore, Petitioner’s arguments on
IPR2014-00652
Patent 6,723,340 B2

41
these items go to the weight to be accorded to the evidence. The Board is
capable of determining and assigning the appropriate weight to the evidence.
For these reasons, we deny Petitioner’s motion.
B. Patent Owner’s Motion to Exclude
Patent Owner filed a Motion to Exclude Evidence seeking to exclude
Exhibits 1030 and 1031 as constituting inadmissible new prior art. PO Mot.
Exclude. Patent Owner further seeks to exclude Exhibit 1021 as irrelevant
and prejudicial. Id. at 1. Petitioner opposes Patent Owner’s Motion, arguing
that (1) Exhibits 1030 and 1031 were submitted with Petitioner’s Reply as
proper rebuttal evidence to arguments made Patent Owner’s Response, and
(2) the Office Patent Trial Practice Guide (77 Fed. Reg. 48,756, 48,764
(Aug. 14, 2012)) allows a Petitioner to attach claim charts from another
proceeding to its Petition (such as Exhibit 1021). Pet. Exclude Opp., 1.
Patent Owner’s arguments on these items go to the weight to be
accorded to the evidence. It is within our discretion to assign the appropriate
weight to be accorded to evidence. See, e.g., Yorkey v. Diab, 601 F.3d 1279,
1284 (Fed. Cir. 2010) (holding the Board has discretion to give more weight
to one item of evidence over another “unless no reasonable trier of fact could
have done so”); In re Am. Acad. of Sci. Tech Ctr., 367 F.3d 1359, 1368 (Fed.
Cir. 2004) (“[T]he Board is entitled to weigh the declarations and conclude
that the lack of factual corroboration warrants discounting the opinions
expressed in the declarations.”); Velander v. Garner, 348 F.3d 1359, 1371
(Fed. Cir. 2003) (“In giving more weight to prior publications than to
subsequent conclusory statements by experts, the Board acted well within
[its] discretion.”). The Board is capable of determining and assigning the
appropriate weight to the evidence.
IPR2014-00652
Patent 6,723,340 B2

42
For this reason, we deny Patent Owner’s Motion to Exclude Exhibits
1030 and 1031.
Additionally, on this record, we need not decide Patent Owner’s
Motion regarding Ex. 1021, because our analysis does not rely upon the
information in that particular exhibit. Consequently, Patent Owner’s Motion
to Exclude Exhibit 1021 is dismissed as moot.
IV. CONCLUSION
We conclude Petitioner has shown by a preponderance of the evidence
that claims 1, 3–5, and 10–13 of the ’340 patent are unpatentable under
35 U.S.C. § 103(a) for obviousness over (1) the Shell 1998 publication, and
(2) the Shell 1998 Publication in view of Papadimitriou.
Petitioner’s Motion to Exclude Exhibits 2163 and 2164 is denied.
Patent Owner’s Motion to Exclude Exhibit 1021 is dismissed, and Patent
Owner’s Motion to Exclude Exhibits 1030 and 1031 is denied.
V. ORDER
For the reasons given, it is
ORDERED that, by a preponderance of the evidence, claims 1, 3–5,
and 10–13 of the ’340 patent are unpatentable;
FURTHER ORDERED that Petitioner’s Motion to Exclude Exhibits
2163 and 2164 is denied;
FURTHER ORDERED that Patent Owner’s Motion to Exclude
Exhibit 1021 is dismissed;
FURTHER ORDERED that Patent Owner’s Motion to Exclude
Exhibits 1030 and 1031 is denied;
IPR2014-00652
Patent 6,723,340 B2

43
FURTHER ORDERED that because this is a Final Written Decision,
parties to the proceeding seeking judicial review of the decision must
comply with the notice and service requirements of 37 C.F.R. § 90.2.

FOR PETITIONER:

Bruce Haas
Henry Renk
Stephen Yam
Christopher Hill
FITZPATRICK, CELLA, HARPER & SCINTO
bhaas@fchs.com
hrenk@fchs.com
syam@fchs.com
chill@fchs.com
Endo-IPR@fchs.com

FOR PATENT OWNER:

Arlene Chow
Eric Lobenfeld
Peter Noh
Ernest Yakob
HOGAN LOVELLS US LLP
arlene.chow@hoganlovells.com
eric.lobenfeld@hoganlovells.com
peter.noh@hoganlovells.com
ernest.yakob@hoganlovells.com